We intend to define the participation of locally generated angiotensin and prostaglandins in regulating vascular tone and modulating sympathetic nervous activity in several vascular beds (splenic, pancreatic, renal and mesenteric) of rabbit, rat and cat. We plan to examine the following: 1) the renin-angiotensin system as a modulator of sympathetic activity. We will investigate the action of angiotensin III and its precursors on the vascular tone and reactivity to adrenergic stimuli. Changes in the latter will be related to alterations in various adrenergic mechanisms. The inhibitors of renin-angiotensin system will be used to define the effects of endogenously generated angiotensins. 2) prostaglandins as modulators of sympathetic activity. 3) Interaction of the renin-angiotensin, prostaglandin and adrenergic nervous system. We will define the effects of exogenous as well as endogenous angiotensins on the release of prostaglandins from perfused organs and consequences of this action on sympathetic activity. We expect, thereby, to define interaction of neural and hormonal elements of a system which may play an important role in the regulation of vascular tone and blood pressure. The Undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.